反应详情

温度

130 °C

A mixture of N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-iodophenyl)benzoxazole-4-carboxamide (35 mg, 0.074 mmol), phenol (14 mg, 0.15 mmol), copper(I) bromide (2 mg, 0.014 mmol), cesium carbonate (49 mg, 0.15 mmol) and pyridine (1 mL) was heated at 130° C. under nitrogen overnight, and then was cooled to room temperature, quenched with saturated sodium bicarbonate, extracted with methylene chloride. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The crude material was purified by semi-preparative HPLC to afford N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-phenoxyphenyl)benzoxazole-4-carboxamide (16 mg, 50%) as a light yellow solid: 1H NMR (500 MHz, CDCl3) δ 9.66 (d, J=7.0 Hz, 1H), 8.20-8.17 (m, 3H), 7.70 (dd, J=8.0, 1.0 Hz, 1H), 7.47-7.42 (m, 3H), 7.23 (t, J=8.0 Hz, 1H), 7.14-7.11 (m, 4H), 4.35-4.28 (m, 1H), 3.52 (ddd, J=14.0, 9.5, 2.0 Hz, 1H), 3.09-2.81 (m, 5H), 2.17-2.07 (m, 2H), 1.80-1.62 (m, 3H); MS (ESI+) m/z 440 (M+H); HPLC>99% (AUC), tR=13.81 min.

1. temperaturewas cooled to room temperature
2. customquenched with saturated sodium bicarbonate
3. extractionextracted with methylene chloride
4. washThe combined organic layers were washed with brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude material was purified by semi-preparative HPLC